Smenamides A and B, Chlorinated Peptide/Polyketide Hybrids Containing a Dolapyrrolidinone Unit from the Caribbean Sponge Smenospongia aurea. Evaluation of Their Role as Leads in Antitumor Drug Research

Abstract

An in-depth study of the secondary metabolites contained in the Caribbean sponge Smenospongia aurea led to the isolation of smenamide A (1) and B (2), hybrid peptide/polyketide compounds containing a dolapyrrolidinone unit. Their structures were elucidated using high-resolution ESI-MS/MS and homo- and heteronuclear 2D NMR experiments. Structures of smenamides suggested that they are products of the cyanobacterial metabolism, and 16S rRNA metagenomic analysis detected Synechococcus spongiarum as the only cyanobacterium present in S. aurea. Smenamides showed potent cytotoxic activity at nanomolar levels on lung cancer Calu-1 cells, which for compound 1 is exerted through a clear pro-apoptotic mechanism. This makes smenamides promising leads for antitumor drug design.

Symbiotic Microbes from Marine Invertebrates: Driving a New Era of Natural Product Drug Discovery

“…This in depth examination led to the elucidation of structures of the two smenamides, and these smenamides appeared to be the products of cyanobacterial metabolism. Indeed further 16S rRNA metagenomic analysis detected Synechococcus spongiarum as the only cyanobacterium present in S. aurea and thus the likely producer of these anti-tumorigenic compounds [50]. Further study on the same sponge species revealed two further anti-tumorigenic compounds, this time with selectivity for ovarian cancer cells.…”

Cytotoxicity of Endoperoxides from the Caribbean Sponge Plakortis halichondrioides towards Sensitive and Multidrug-Resistant Leukemia Cells: Acids vs. Esters Activity Evaluation

“…Marine organisms are excellent sources of novel skeletons ranging from small terpene molecules [1,2], mixed polyketide-peptide biogenesis [3,4], to more complex carbohydrate-based scaffolds [5,6]. Many of these novel skeletons [7] have been tested for their possible role as lead compounds in the search for new drugs for various diseases.…”

Quorum Sensing Inhibitors from the Sea Discovered Using Bacterial N-acyl-homoserine Lactone-Based Biosensors

“…In 2014 alone, 283 new compound structures reported from sponges enabled the phylum to regain its position as the dominant source of new bioactive metabolites [75]. Compounds range from terpene skeletons, mixed polyketide-peptide biogenesis molecules to complex carbohydrate-based metabolites [89,90,91,92,93]. Many of these metabolites have been tested for their possible role as lead compounds in drug research.…”